Zika May Increase Risk of Mental Illness, Researchers Say

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A pregnant woman waits for an examination for mosquito-borne viruses like Zika at a maternity ward in Honduras. Experts say the Zika virus closely resembles some infectious agents that have been linked to autism, bipolar disorder and schizophrenia.CreditCreditJorge Cabrera/Reuters

A baby with a shrunken, misshapen head is surely a heartbreaking sight. But reproductive health experts are warning that microcephaly may be only the most obvious consequence of the spread of the Zika virus.

Even infants who appear normal at birth may be at higher risk for mental illnesses later in life if their mothers were infected during pregnancy, many researchers fear.

The Zika virus, they say, closely resembles some infectious agents that have been linked to the development of autism, bipolar disorder and schizophrenia.

Schizophrenia and other debilitating mental illnesses have no single cause, experts emphasized in interviews. The conditions are thought to arise from a combination of factors, including genetic predisposition and traumas later in life, such as sexual or physical abuse, abandonment or heavy drug use.

But illnesses in utero, including viral infections, are thought to be a trigger.

Among children in Latin America and the Caribbean, “I wouldn’t be surprised if we saw a big upswing in A.D.H.D., autism, epilepsy and schizophrenia,” he added. “We’re looking at a large group of individuals who may not be able to function in the world.”

A viral attack early in pregnancy can kill a fetus or stunt the growing brain, producing microcephaly, they said. An infection later in the fetus’s development, when the brain is nearly fully formed, can do damage that is less obvious but still significant.

“It is pretty scary,” said Dr. Urs Meyer, a behavioral neurobiologist at the Swiss Federal Institute of Technology in Zurich who studies the consequences of fetal infections in laboratory animals. “These problems are on a continuous scale, and whether you end up with autism or schizophrenia is complex — and we really can’t predict it.”

Evidence has increased for years that mental illnesses may be linked to exposure during pregnancy to viruses like rubella, herpes and influenza, and to parasites like Toxoplasma gondii.

“It can happen with a variety of viruses and other infectious agents, but we don’t know how often,” said Dr. E. Fuller Torrey, the executive director of the Stanley Medical Research Institute in Chevy Chase, Md.

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W. Ian Lipkin, who directs the Center for Infection and Immunity at Columbia University, warned of an upswing in A.D.H.D., autism, epilepsy and schizophrenia tied to Zika.CreditJoshua Bright for The New York Times

Dr. Torrey noted that Rosemary Kennedy, sister of President of John F. Kennedy, was born in 1918 during the Spanish flu epidemic. She had mental disabilities as a child and developed schizophrenia-like symptoms at age 20. Although some historians have attributed her disabilities to a lack of oxygen at birth, Dr. Torrey believes that viral infection in utero is “the most likely” explanation.

But estimates of the size of the risk vary. One 2011 analysis of other studies estimated that maternal infections of any kind account for 6 percent of all cases of schizophrenia. (Researchers have done very large studies in Finland, Sweden and Denmark because they have cradle-to-grave records on millions of citizens.)

By contrast, a 2001 study of adults born to mothers infected with rubella, or German measles, during the last American epidemic, which lasted from 1964 to 1965, found that 20 percent had schizophrenia symptoms. The expected rate among adults is below 1 percent.

Dr. Alan S. Brown, the director of birth cohort studies at Columbia University Medical School and leader of that study, said it was “certainly possible” that Zika posed a similar risk, “although ideally, you’d want a controlled study.”

Although children may be troubled, the hallucinations, voices and paranoia of true schizophrenia do not normally emerge until late adolescence, “when there is a lot of rearranging and pruning in the brain,” said Dr. Robert H. Yolken, a developmental neurovirologist at Johns Hopkins University, who also believes that Zika increases mental illness risk.

The effects of Zika mimic those of rubella, some experts noted: Both cause only a mild rash in adults, but can cause stillbirths, microcephaly and eye malformations in newborns.

In the 1964-65 rubella epidemic, about 20,000 newborns suffered consequences: A total of 11,000 were born deaf, 3,500 were born blind, and at least 1,800 were later found to have mental problems.

That epidemic infected an estimated 12 million Americans. More than 500 million people live in the countries of Latin America and the Caribbean to which the World Health Organization has predicted that Zika will spread.

Dr. Stanley A. Plotkin, a rubella expert, said it was possible that children who survived maternal Zika infections with no signs of microcephaly could still display mental deficits as they grow.

“Any virus in the blood of a pregnant woman is a risk to the fetus, so ultimately there may be damage,” he said. His own work as a pediatrician showed that many children who survived the 1964-65 epidemic “suffered from autism, learning disabilities and behavioral disabilities.”

The Zika virus seems to zero in on nerve cells even more than does rubella, which also causes heart defects, for example.

Pathologists in Ljubljana, Slovenia, who dissected a microcephalic fetus aborted at 32 weeks by a European woman who had become pregnant in Brazil reported last week that they found “severe fetal brain injury associated with ZIKV infection with vertical transmission” — meaning the Zika virus had come from the mother’s infection.

Flu viruses do not cross the placenta, Dr. Meyer of the Swiss Institute said, but the mother’s immune reaction creates a storm of cytokines, some of which do. Cytokines are small “signaling” proteins that can cause cells to stop growing.

How much damage is done depends not just on the virus and the mother’s immune response, but at which stage of pregnancy the infection strikes.

First-trimester infections may cause brain tissue to calcify and die; later ones may have subtler, but still insidious, effects.

For example, Dr. Lipkin of the Columbia immunity center said that his lab in 2010 infected pregnant mice with a synthetic RNA virus that replicated in fetal mouse brains. The results were wildly unpredictable.

“If you infected them halfway through gestation, the offspring were withdrawn; they sat in a corner of their cage and didn’t interact at all,” he said. “If you did it two-thirds of the way through, they were hyperactive.”

Reports suggest that Brazil, which was facing economic crises even before the Zika outbreak, has little capacity to cope with a surge of mentally disabled children.

European researchers initially paid little attention to the South American outbreak, Dr. Meyer said. But that has changed.

“The information we’re hearing now is just overwhelming,” he said. “A whole generation of children might be affected.”